Method and Composition for Administering Bioactive Compounds Derived From Morinda Citrifolia

ABSTRACT

This invention relates to a method and composition for providing in various health benefits by administering various bioactive compounds derived from the plant  Morinda cirtrifolia  to individuals. This invention relates to using one or more of the following: Noni Leaf Extract; Noni Leaf Juice; and/or Roast Leaf More particularly this invention relates to administering one or more of the following: Pyro-phorbide a, Pheophorbide a, Purpin 7, and/or Pheophorbide all which may be derived from Noni leaf extract, Noni leaf juice, and/or Roast leaf Moreover, the foregoing formulations result in alleviating pain and inflammation.

RELATED APPLICATIONS

This application claims priority to U.S. Patent Application Ser. No.60/799,793 filed May 12, 2006 and entitled “Method and Composition forAdministering Bioactive Compounds Derived from Morinda Citrifolia.”

BACKGROUND

1. Field of Invention

This invention relates to a method and composition for providing invarious health benefits by administering various bioactive compoundsderived from the plant Morinda cirtrifolia to individuals. Moreparticularly this invention relates to administering one or more of thefollowing: Pyro-phorbide a, Pheophorbide a, Purpin 7, and/orPheophorbide Phypolesper all which may be derived from Noni leafextract, Noni leaf juice, and/or Roast leaf. Moreover, the foregoingformulations result in alleviating pain and inflammation.

2. Background

People are becoming increasingly more conscientious of their health.With a variety of deadly diseases and ailments threatening the publichealth each year, efforts to find treatments and medications that treatand prevent disease are ongoing. Moreover, studies show thatcomprehensive, novel early prevention and detection strategies increasehealthy life potential.

SUMMARY AND OBJECTS OF THE INVENTION

Some embodiments of this invention relate to methods and compositionsfor providing various health benefits by administering bioactivecompounds derived from the plant Morinda cirtrifolia to individuals.

Some embodiments relate to using one or more of the following: Noni LeafExtract; Noni Leaf Juice; and/or Roast Leaf to inhibit the following:HMG-CoA Reductase; Phosphodiesterases (3 and 4) PDE3 and PDE4;5-Lipoxygenase (LOX) and 15-LOX; Xanthine Oxidase (X0); Gamma AminoButyric Acid (GABA) and the growth of the second most common human skincancer cell line.

Some embodiments relate to administering one or more of the following:Pyro-phorbide a, Pheophorbide a, Purpin 7, and/or PheophorbidePhypolesper all which may be derived from Noni leaf extract, Noni leafjuice, and/or Roast leaf.

Some embodiments result in alleviating pain and inflammation.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The objects and features of the present invention will become more fullyapparent from the following description and appended claims, taken inconjunction with the accompanying drawings. Understanding that thesedrawings depict only typical embodiments of the invention and are,therefore, not to be considered limiting of its scope, the inventionwill be described and explained with additional specificity and detailthrough the use of the accompanying drawings in which:

FIG. 1 shows an example of a concentration-response curve for inhibitionof growth in A431 human tumor cell line treated with Leaf Extract;

FIG. 2 shows an example of a concentration-response curve for inhibitionof growth in A431 human tumor cell line treated with Leaf Juice; and

FIG. 3 shows an example of a concentration-response curve for inhibitionof growth in A431 human tumor cell line treated with Leaf Roast.

DETAILED DESCRIPTION OF THE INVENTION

It will be readily understood that the components of the presentinvention, as generally described herein, could be arranged and designedin a wide variety of different configurations. Thus, the following moredetailed description of embodiments of the compositions and methods ofthe present invention is not intended to limit the scope of theinvention, as claimed, but is merely representative of the presentlypreferred embodiments of the invention. The scope of the invention is,therefore, indicated by the appended claims rather than by the foregoingdescription. All changes that come within the meaning and range ofequivalency of the claims are to be embraced within their scope.

This invention relates to a method and composition for providing invarious health benefits by administering various bioactive compoundsderived from the plant Morinda cirtrifolia to individuals. Thisinvention relates to using one or more of the following: Noni LeafExtract; Noni Leaf Juice; and/or Roast Leaf to inhibit the following:HMG-CoA Reductase; Phosphodiesterases (3 and 4) PDE3 and PDE4;5-Lipoxygenase (LOX) and 15-LOX; Xanthine Oxidase (X0); Gamma AminoButyric Acid (GABA) and the growth of the second most common human skincancer cell line. More particularly this invention relates toadministering one or more of the following: Pyro-phorbide a,Pheophorbide a, Purpin 7, and/or Pheophorbide Phypolesper all which maybe derived from Noni leaf extract, Noni leaf juice, and/or Roast leaf.Moreover, the foregoing formulations result in alleviating pain andinflammation.

General Description of the Morinda citrifolia L. Plant The IndianMulberry or Morinda citrifolia plant, known scientifically as MorindaCitrifolia L. (“Morinda citrifolia”), is a shrub or small tree up to 10m in height. The leaves are oppositely arranged with an elliptic toovate form. The small white flowers are contained in a fleshy, globose,head like cluster. The fruits are large, fleshy, and ovoid. At maturity,they are creamy white and edible, but have an unpleasant taste and odor.The plant is native to Southeast Asia and has spread in early times to avast area from India to eastern Polynesia. It grows randomly in thewild, and it has been cultivated in plantations and small individualgrowing plots. The Morinda citrifolia flowers are small, white, three tofive lobed, tubular, fragrant, and about 1.25 cm long. The flowersdevelop into compound fruits composed of many small drupes fused into anovoid, ellipsoid or roundish, lumpy body, with waxy, white, orgreenish-white or yellowish, semi-translucent skin. The fruit contains“eyes” on its surface, similar to a potato. The fruit is juicy, bitter,dull-yellow or yellowish-white, and contains numerous red-brown, hard,oblong-triangular, winged 2-celled stones, each containing four seeds.When fully ripe, the fruit has a pronounced odor like rancid cheese.Although the fruit has been eaten by several nationalities as food, themost common use of the Morinda citrifolia plant has traditionally beenas a red and yellow dye source.

The Morinda citrifolia plant is rich in natural ingredients. Thoseingredients that have been discovered include from the leaves: alanine,anthraquinones, arginine, ascorbic acid, aspartic acid, calcium, betacarotene, cysteine, cystine, glycine, glutamic acid, glycosides,histidine, iron, leucine, isoleucine, methionine, niacin, phenylalanine,phosphorus, proline, resins, riboflavin, serine, beta sitosterol,thiamine, threonine, tryptophan, tyrosine, ursolic acid, and valine;from the flowers: acacetin 7 o beta d (+) glucopyranoside, 5,7 dimethylapigenin 4′ o beta d(+) galactopyranoside, and 6,8 dimethoxy 3methylanthraquinone 1 o beta rhamnosyl glucopyranoside; from the fruit:acetic acid, asperuloside, butanoic acid, benzoic acid, benzyl alcohol,1 butanol, caprylic acid, decanoic acid, (E) 6 dodeceno gamma lactone,(Z,Z,Z) 8,11,14 eicosatrienoic acid, elaidic acid, ethyl decanoate,ethyl hexanoate, ethyl octanoate, ethyl palmitate, (Z) 6(ethylthiomethyl)benzene, eugenol, glucose, heptanoic acid, 2 heptanone,hexanal, hexanamide, hexanedioic acid, hexanoic acid (hexoic acid), 1hexanol, 3 hydroxy 2 butanone, lauric acid, limonene, linoleic acid, 2methylbutanoic acid, 3 methyl 2 buten 1 ol, 3 methyl 3 buten 1 ol,methyl decanoate, methyl elaidate, methyl hexanoate, methyl 3 methylthiopropanoate, methyl octanoate, methyl oleate, methyl palmitate, 2methylpropanoic acid, 3 methylthiopropanoic acid, myristic acid,nonanoic acid, octanoic acid (octoic acid), oleic acid, palmitic acid,potassium, scopoletin, undecanoic acid, (Z,Z) 2,5 undecadien 1 ol, andvomifol; from the roots: anthraquinones, asperuloside (rubichloricacid), damnacanthal, glycosides, morindadiol, morindine, morindone,mucilaginous matter, nor damnacanthal, rubiadin, rubiadin monomethylether, resins, soranjidiol, sterols, and trihydroxymethyl anthraquinonemonomethyl ether; from the root bark: alizarin, chlororubin, glycosides(pentose, hexose), morindadiol, morindanigrine, morindine, morindone,resinous matter, rubiadin monomethyl ether, and soranjidiol; from thewood: anthragallol 2,3 dimethylether; from the tissue culture:damnacanthal, lucidin, lucidin 3 primeveroside, and morindone 6betaprimeveroside; from the plant: alizarin, alizarin alpha methyl ether,anthraquinones, asperuloside, hexanoic acid, morindadiol, morindone,morindogenin, octanoic acid, and ursolic acid.

Processing Morinda citrifolia Leaves

The leaves of the Morinda citrifolia plant are one possible component ofthe Morinda citrifolia plant that may be present in some compositions ofthe present invention. For example, some compositions comprise leafextract and/or leaf juice as described further herein. Some compositionscomprise a leaf serum that is comprised of both leaf extract and fruitjuice obtained from the Morinda citrifolia plant. Some compositions ofthe present invention comprise leaf serum and/or various leaf extractsas incorporated into a nutraceutical product (“nutraceutical” hereinreferring to any drug or product designed to improve the health ofliving organisms such as human beings or mammals).

In some embodiments of the present invention, the Morinda citrifolialeaf extracts are obtained using the following process. First,relatively dry leaves from the Morinda citrifolia L. plant arecollected, cut into small pieces, and placed into a crushingdevice—preferably a hydraulic press—where the leaf pieces are crushed.In some embodiments, the crushed leaf pieces are then percolated with analcohol such as ethanol, methanol, ethyl acetate, or other alcohol-basedderivatives using methods known in the art. Next, in some embodiments,the alcohol and all alcohol-soluble ingredients are extracted from thecrushed leaf pieces, leaving a leaf extract that is then reduced withheat to remove all the liquid therefrom. The resulting dry leaf extractwill herein be referred to as the “primary leaf extract.”

In some embodiments of the present invention, the primary leaf extractis pasteurized to at least partially sterilize the extract and destroyobjectionable organisms. The primary leaf extract is pasteurizedpreferably at a temperature ranging from 70 to 80 degrees Celsius andfor a period of time sufficient to destroy any objectionable organismswithout major chemical alteration of the extract. Pasteurization mayalso be accomplished according to various radiation techniques ormethods.

In some embodiments of the present invention, the pasteurized primaryleaf extract is placed into a centrifuge decanter where it iscentrifuged to remove or separate any remaining leaf juice therein fromother materials, including chlorophyll. Once the centrifuge cycle iscompleted, the leaf extract is in a relatively purified state. Thispurified leaf extract is then pasteurized again in a similar manner asdiscussed above to obtain a purified primary leaf extract.

Preferably, the primary leaf extract, whether pasteurized and/orpurified, is further fractionated into two individual fractions: a dryhexane fraction, and an aqueous methanol fraction. This is accomplishedpreferably via a gas chromatograph containing silicon dioxide andCH2C12-MeOH ingredients using methods well known in the art. In someembodiments of the present invention, the methanol fraction is furtherfractionated to obtain secondary methanol fractions. In someembodiments, the hexane fraction is further fractionated to obtainsecondary hexane fractions.

One or more of the leaf extracts, including the primary leaf extract,the hexane fraction, methanol fraction, or any of the secondary hexaneor methanol fractions may be combined with the fruit juice of the fruitof the Morinda citrifolia plant to obtain a leaf serum (the process ofobtaining the fruit juice to be described further herein). In someembodiments, the leaf serum is packaged and frozen ready for shipment;in others, it is further incorporated into a nutraceutical product asexplained herein.

Processing Morinda citrifolia Fruit

Some embodiments of the present invention include a compositioncomprising fruit juice of the Morinda citrifolia plant. Because theMorinda citrifolia fruit is for all practical purposes inedible, thefruit must be processed in order to make it palatable for humanconsumption and included in the compositions of the present invention.Processed Morinda citrifolia fruit juice can be prepared by separatingseeds and peels from the juice and pulp of a ripened Morinda citrifoliafruit; filtering the pulp from the juice; and packaging the juice.Alternatively, rather than packaging the juice, the juice can beimmediately included as an ingredient in another product, frozen orpasteurized. In some embodiments of the present invention, the juice andpulp can be pureed into a homogenous blend to be mixed with otheringredients. Other processes include freeze drying the fruit and juice.The fruit and juice can be reconstituted during production of the finaljuice product. Still other processes may include air drying the fruitand juices prior to being masticated.

In a currently preferred process of producing Morinda citrifolia fruitjuice, the fruit is either hand picked or picked by mechanicalequipment. The fruit can be harvested when it is at least one inch (2-3cm) and up to 12 inches (24-36 cm) in diameter. The fruit preferably hasa color ranging from a dark green through a yellow-green up to a whitecolor, and gradations of color in between. The fruit is thoroughlycleaned after harvesting and before any processing occurs.

The fruit is allowed to ripen or age from 0 to 14 days, but preferablyfor 2 to 3 days. The fruit is ripened or aged by being placed onequipment so that the fruit does not contact the ground. The fruit ispreferably covered with a cloth or netting material during aging, butthe fruit can be aged without being covered. When ready for furtherprocessing the fruit is light in color, such as a light green, lightyellow, white or translucent color. The fruit is inspected for spoilageor for excessive green color and firmness. Spoiled and hard green fruitis separated from the acceptable fruit.

The ripened and aged fruit is preferably placed in plastic linedcontainers for further processing and transport. The containers of agedfruit can be held from 0 to 30 days, but preferably the fruit containersare held for 7 to 14 days before processing. The containers canoptionally be stored under refrigerated conditions prior to furtherprocessing. The fruit is unpacked from the storage containers and isprocessed through a manual or mechanical separator. The seeds and peelare separated from the juice and pulp.

The juice and pulp can be packaged into containers for storage andtransport. Alternatively, the juice and pulp can be immediatelyprocessed into a finished juice product. The containers can be stored inrefrigerated, frozen, or room temperature conditions. The Morindacitrifolia juice and pulp are preferably blended in a homogenous blend,after which they may be mixed with other ingredients, such asflavorings, sweeteners, nutritional ingredients, botanicals, andcolorings. The finished juice product is preferably heated andpasteurized at a minimum temperature of 181° F. (83° C.) or higher up to212° F. (100° C.). Another product manufactured is Morinda citrifoliapuree and puree juice, in either concentrate or diluted form. Puree isessentially the pulp separated from the seeds and is different than thefruit juice product described herein.

The product is filled and sealed into a final container of plastic,glass, or another suitable material that can withstand the processingtemperatures. The containers are maintained at the filling temperatureor may be cooled rapidly and then placed in a shipping container. Theshipping containers are preferably wrapped with a material and in amanner to maintain or control the temperature of the product in thefinal containers.

The juice and pulp may be further processed by separating the pulp fromthe juice through filtering equipment. The filtering equipmentpreferably consists of, but is not limited to, a centrifuge decanter, ascreen filter with a size from 1 micron up to 2000 microns, morepreferably less than 500 microns, a filter press, a reverse osmosisfiltration device, and any other standard commercial filtration devices.The operating filter pressure preferably ranges from 0.1 psig up toabout 1000 psig. The flow rate preferably ranges from 0.1 g.p.m. up to1000 g.p.m., and more preferably between 5 and 50 g.p.m. The wet pulp iswashed and filtered at least once and up to 10 times to remove any juicefrom the pulp. The resulting pulp extract typically has a fiber contentof 10 to 40 percent by weight. The resulting pulp extract is preferablypasteurized at a temperature of 181° F. (83° C.) minimum and then packedin drums for further processing or made into a high fiber product.

Processing Morinda citrifolia Seeds

Some Morinda citrifolia compositions of the present invention includeseeds from the Morinda citrifolia plant. In some embodiments of thepresent invention, Morinda citrifolia seeds are processed by pulverizingthem into a seed powder in a laboratory mill. In some embodiments, theseed powder is left untreated. In some embodiments, the seed powder isfurther defatted by soaking and stirring the powder in hexane—preferablyfor 1 hour at room temperature (Drug:Hexane—Ratio 1:10). The residue, insome embodiments, is then filtered under vacuum, defatted again(preferably for 30 minutes under the same conditions), and filteredunder vacuum again. The powder may be kept overnight in a fume hood inorder to remove the residual hexane.

Still further, in some embodiments of the present invention, thedefatted and/or untreated powder is extracted, preferably with ethanol50% (m/m) for 24 hours at room temperature at a drug solvent ratio of1:2.

Processing Morinda citrifolia Oil

Some embodiments of the present invention may comprise oil extractedfrom the Morinda Citrifolia plant. The method for extracting andprocessing the oil is described in U.S. patent application Ser. No.09/384,785, filed on Aug. 27, 1999 and issued as U.S. Pat. No. 6,214,351on Apr. 10, 2001, which is incorporated by reference herein. The Morindacitrifolia oil typically includes a mixture of several different fattyacids as triglycerides, such as palmitic, stearic, oleic, and linoleicfatty acids, and other fatty acids present in lesser quantities. Inaddition, the oil preferably includes an antioxidant to inhibit spoilageof the oil. Conventional food grade antioxidants are preferably used.

Compositions and Their Use

This invention relates to a method and composition for providing invarious health benefits by administering various bioactive compoundsderived from the plant Morinda cirtrifolia to individuals. Thisinvention relates to using one or more of the following: Noni LeafExtract; Noni Leaf Juice; and/or Roast Leaf to inhibit the following:HMG-CoA Reductase; Phosphodiesterases (3 and 4) PDE3 and PDE4;5-Lipoxygenase (LOX) and 15-LOX; Xanthine Oxidase (X0); Gamma AminoButyric Acid (GABA) and the growth of the second most common human skincancer cell line. More particularly this invention relates toadministering one or more of the following: Pyro-phorbide a,Pheophorbide a, Purpin 7, and/or Pheophorbide Phypolesper all which maybe derived from Noni leaf extract, Noni leaf juice, and/or Roast leaf.Moreover, the foregoing formulations result in alleviating pain andinflammation.

Compositions of the present invention may comprise any of a number ofMorinda citrifolia components such as: leaf extract, leaf juice, leafserum, fruit juice, fruit pulp, pulp extract, puree, seeds (whetherdefatted or untreated), and oil. Compositions of the present inventionmay also include various other ingredients. Examples of otheringredients include, but are not limited to: artificial flavoring, othernatural juices or juice concentrates such as a natural grape juiceconcentrate or a natural blueberry juice concentrate; carrieringredients; and others as will be further explained herein.

Any compositions having the leaf extract from the Morinda citrifolialeaves, may comprise one or more of the following: the primary leafextract, the hexane fraction, methanol fraction, the secondary hexaneand methanol fractions, the leaf serum, or the nutraceutical leafproduct.

In some embodiments of the present invention, active ingredients orcompounds of Morinda citrifolia components may be extracted out usingvarious procedures and processes commonly known in the art. Forinstance, the active ingredients may be isolated and extracted out usingalcohol or alcohol-based solutions, such as methanol, ethanol, and ethylacetate, and other alcohol-based derivatives using methods known in theart. These active ingredients or compounds may be isolated and furtherfractioned or separated from one another into their constituent parts.Preferably, the compounds are separated or fractioned to identify andisolate any active ingredients that might help to prevent disease,enhance health, or perform other similar functions. In addition, thecompounds may be fractioned or separated into their constituent parts toidentify and isolate any critical or dependent interactions that mightprovide the same health-benefiting functions just mentioned.

Any components and compositions of Morinda citrifolia may be furtherincorporated into a nutraceutical product (again, “nutraceutical” hereinreferring to any drug or product designed to improve the health ofliving organisms such as human beings or mammals). Examples ofnutraceutical products may include, but are not limited to: intravenousproducts, topical dermal products, wound healing products, skin careproducts, hair care products, beauty and cosmetic products (e.g.,makeup, lotions, etc.), burn healing and treatment products, first-aidproducts, antibacterial products, lip balms and ointments, bone healingand treatment products, meat tenderizing products, anti-inflammatoryproducts, eye drops, deodorants, antifungal products, arthritistreatment products, muscle relaxers, toothpaste, and variousnutraceutical and other products as may be further discussed herein.

The compositions of the present invention may be formulated into any ofa variety of embodiments, including oral compositions, topical dermalsolutions, intravenous solutions, and other products or compositions.

Oral compositions may take the form of, for example, tablets, lozenges,aqueous or oily suspensions, dispersible powders or granules, emulsions,syrups, or elixirs. Compositions intended for oral use may be preparedaccording to any method known in the art, and such compositions maycontain one or more agents such as sweetening agents, flavoring agents,coloring agents, and preserving agents. They may also contain one ormore additional ingredients such as vitamins and minerals, etc. Tabletsmay be manufactured to contain one or more Morinda citrifolia componentsin admixture with non-toxic, pharmaceutically acceptable excipients thatare suitable for the manufacture of tablets. These excipients may be,for example, inert diluents, granulating and disintegrating agents,binding agents, and lubricating agents. The tablets may be uncoated orthey may be coated by known techniques to delay disintegration andabsorption in the gastrointestinal tract and thereby provide sustainedaction over a longer period. For example, a time delay material such asglyceryl monostearate or glyceryl distearate may be used.

Aqueous suspensions may be manufactured to contain the Morindacitrifolia components in admixture with excipients suitable for themanufacture of aqueous suspensions. Examples of such excipients include,but are not limited to: suspending agents such as sodiumcarboxymethyl-cellulose, methylcellulose, hydroxy-propylmethycellulose,sodium alginate, polyvinyl-pyrrolidone, gum tragacanth and gum acacia;dispersing or wetting agents such as a naturally-occurring phosphatidelike lecithin, or condensation products of an alkylene oxide with fattyacids such as polyoxyethylene stearate, or condensation products ofethylene oxide with long chain aliphatic alcohols such asheptadecaethylene-oxycetanol, or condensation products of ethylene oxidewith partial esters derived from fatty acids and a hexitol such aspolyoxyethylene sorbitor monooleate, or condensation products ofethylene oxide with partial esters derived from fatty acids and hexitolanhydrides such as polyethylene sorbitan monooleate.

Typical sweetening agents may include, but are not limited to: naturalsugars derived from corn, sugar beets, sugar cane, potatoes, tapioca, orother starch-containing sources that can be chemically or enzymaticallyconverted to crystalline chunks, powders, and/or syrups. Also,sweeteners can comprise artificial or high-intensity sweeteners, some ofwhich may include aspartame, sucralose, stevia, saccharin, etc. Theconcentration of sweeteners may be between from 0 to 50 percent byweight of the Morinda citrifolia composition, and more preferablybetween about 1 and 5 percent by weight.

Typical flavoring agents can include, but are not limited to, artificialand/or natural flavoring ingredients that contribute to palatability.The concentration of flavors may range, for example, from 0 to 15percent by weight of the Morinda citrifolia composition. Coloring agentsmay include food-grade artificial or natural coloring agents having aconcentration ranging from 0 to 10 percent by weight of the Morindacitrifolia composition.

Typical nutritional ingredients may include vitamins, minerals, traceelements, herbs, botanical extracts, bioactive chemicals, and compoundsat concentrations from 0 to 10 percent by weight of the Morindacitrifolia composition. Examples of vitamins include, but are notlimited to, vitamins A, B1 through B12, C, D, E, Folic Acid, PantothenicAcid, Biotin, etc. Examples of minerals and trace elements include, butare not limited to, calcium, chromium, copper, cobalt, boron, magnesium,iron, selenium, manganese, molybdenum, potassium, iodine, zinc,phosphorus, etc. Herbs and botanical extracts may include, but are notlimited to, alfalfa grass, bee pollen, chlorella powder, Dong Quaipowder, Ecchinacea root, Gingko Biloba extract, Horsetail herb, Indianmulberry, Shitake mushroom, spirulina seaweed, grape seed extract, etc.Typical bioactive chemicals may include, but are not limited to,caffeine, ephedrine, L-carnitine, creatine, lycopene, etc.

The ingredients to be utilized in a topical dermal product may includeany that are safe for internalizing into the body of a mammal and mayexist in various forms, such as gels, lotions, creams, ointments, etc.,each comprising one or more carrier agents. The ingredients or carrieragents incorporated into systemically (e.g., intravenously) administeredcompositions may also comprise any known in the art.

In one exemplary embodiment, a Morinda citrifolia composition of thepresent invention comprises one or more of a processed Morindacitrifolia component present in an amount by weight between about 0.01and 100 percent by weight, and preferably between 0.01 and 95 percent byweight. Several embodiments of formulations are included in U.S. Pat.No. 6,214,351, issued on Apr. 10, 2001. However, these compositions areonly intended to be exemplary, as one ordinarily skilled in the art willrecognize other formulations or compositions comprising the processedMorinda citrifolia product.

In another exemplary embodiment, the internal composition comprises theingredients of: processed Morinda citrifolia fruit juice or puree juicepresent in an amount by weight between about 0.1-80 percent; processedMorinda citrifolia oil present in an amount by weight between about0.1-20 percent; and a carrier medium present in an amount by weightbetween about 20-90 percent. Morinda citrifolia puree juice or fruitjuice may also be formulated with a processed Morinda citrifolia dietaryfiber product present in similar concentrations.

EXAMPLES

The following examples illustrate some of the embodiments of theinvention. These examples are not intended to be limiting in any way,but are merely illustrative of benefits, advantages, and remedialeffects of some embodiments of the Morinda citrifolia compositions ofthe present invention.

Example 1 Noni Leaf Juice

In one example, the effects of Morinda Citrifolia leaf juice on 5-LOXand 15-LOX, HMG-CoA, PDE3 and PDE4, XO and GABA were studied. MorindaCitrifolia leaf juice was administered to rabbits, rats, humans andbovines at various concentration dosages. Inhibition of 5-LOX and 15-LOXwas observed in both rabbits and humans, respectively. Inhibition ofHMG-CoA Reductase was observed in rats. Inhibition of PDEs was observedin humans. Inhibition of xanthine oxidase was observed in bovines andinhibition of GABA was observed in rats. The following tables summarizethe results of these studies.

TABLE 1 Example 1 Test Std. Enzyme Animal No. Samples % InhibitionDeviation HMG-CoA Reductase Rat 2 10%  29 2 5% 5 2 1% −3 Lipoxygenase15- Rabbit 2 10%  111 LOX 2 5% 102 2 1% 87 Lipoxygenase 5- Human 2 10% 101 LOX 2 5% 85 2 1% 41 Phosphodiesterase Human 2 10%  71 PDE3 2 5% 33 21% 8 Phosphodiesterase Human 2 10%  94 PDE4 2 5% 45 2 1% 17Phosphodiesterase Human 2 10%  41 PDE5 2 5% 0 2 1% 6 Xanthine OxidaseBovine 2 10%  33 2 5% 29 2 1% 6 GABA₂, Agonist Site Rat 2 10%  105 2 5%104 2 1% 103

Example 2 Noni Leaf Extract

TABLE 2 Example 2 Test % NLEX in Animal No. Samples Solution %Inhibition HMG-CoA Reductase NLEX-P rat 2 0.1% 54 2 0.05%  40 0.025%  7Phophodiestrerase PDE3 NLEX-P hum 2 0.1% 79 2 0.05%  69 2 0.025%  58Phophodiestrerase PDE4 NLEX-P hum 2 0.1% 82 2 0.5% 69 2 0.025%  54Phophodiestrerase PDE5 NLEX-P hum 2 0.1% 87 2 0.05%  84 2 0.025%  77

Example 2 (above) was based on the following parameters:

TABLE 3 HMG-CoA Reductase Source: Wistar Rat liver Substrate:2.504[14C]HMG-CoA Vehicle: 1% DMSO Pre-Incubation Time/Temp: 15 minutes@ 37° C. Incubation Buffer: 100 mM Potassium Phosphate, pH 7.5, 20 mMG-6-P. 2.5 mM NADP 10 mM EDTA 5 mM DTT, 14 U G- 6-P-DH QuantitationMethod: Quantitation of [14C]Mevalonate Significance Criteria: >50% ofmax stimulation or inhibition

TABLE 4 Phosphodiesterase PDE3 Source: Human platelets Substrate:1.01/.2M (PH]cAMP + cAMP) Vehicle: 1% DMSO Pre-Incubation Time/Temp: 15minutes @ 25° C. Incubation Time/Temp: 20 minutes @ 25° C. IncubationBuffer: 50 mM Tris-HCL, pH 7.5.5 mM MgC12 Quantitation Method:Quantitation of (PH) Adenosine Significance Criteria: ≧50% of maxstimulation or inhibition

TABLE 5 Phosphodiesterase PDE4 Source: Human U937 cells Substrate: 1.01MM (PHicAMP + cAMP) Vehicle: 1% DMSO Pre-Incubation Time/Temp: 15minutes @ 25° C. Incubation Time/Temp: 20 minutes @ 25° C. IncubationBuffer: 50 mM Tris-HCL, pH 7.5.5 mM MgC12 Quantitation Method:Quantitation of (PH) Adenosine Significance Criteria: ≧50% of maxstimulation or inhibition

TABLE 6 Phosphodiesterase PDE5 Source: Human platelets Substrate:1.01/zM (PH]cGMP + cGMP) Vehicle: 1% DMSO Pre-Incubation Time/Temp: 15minutes @ 25° C. Incubation Time/Temp: 20 minutes @ 25° C. IncubationBuffer: 50 mM Tris-HCL, pH 7.5.5 mM MgC12 Quantitation Method:Quantitation of (PH) Guanosine Significance Criteria: >50% of maxstimulation or inhibition

Example 3

In this next example, Morinda citrifolia leaf juice and leaf extract wasshown to significantly inhibit the growth of the second most common typeof human skin cancer. In this example, assays were performed to detectchanges in cell proliferation based on the ability of viable cells tocause alamarBlue to change from non-fluorescent blue to a reduced,fluorescent red form. With the results obtained from the alamarBluereaction, cell proliferation can be quantified and metabolic activity ofviable cells can be examined. Test compounds including Morindacitrifolia leaf extract, leaf juice, and roast leaf were tested fortheir effects on the proliferation of human epidermoid carcinoma cellline-A431 at assay concentrations from 0.01 to 100 μg/ml or 0.0001% to1% through serial 10-fold dilutions.

In summary, it was found that the leaf extract at concentrations between10 and 100 μg/ml, as well as the leaf juice between 0.1% and 1%, causedsignificant growth inhibition (<50% of growth) relative to thevehicle-treated control in the tumor cell line—whereas the roast leaffailed to show a significant effect (0.01-100 μg/ml). Significantinhibitory activity was also observed for the concurrently testedstandard reference agent, Mitomycin, at <10 p.M. Consequently,semi-quantitative determinations of estimated LC₅₀ (50% inhibitionconcentration), TGI (total growth inhibition) and LC₅₀ (50% lethalconcentration) by nonlinear regression analysis were calculated.Following is a description of the materials, equipment, and methods usedin the assay, as well as tables summarizing the results.

Test Substances and Concentrations.

Morinda citrifolia leaf extract, leaf juice, and roast leaf wereprovided by Tahitian Noni International, Inc. for in vitro anti-tumorstudies. The Morinda citrifolia compounds were dissolved in steriledistilled water and then diluted with sterile distilled water to obtaininitial working solutions of 10000, 1000, 100, 10, and 1 μg/ml for theleaf extract and roast leaf, as well as 100, 10, 1, 0.1 and 0.01% forthe leaf juice. In testing, 100-fold dilution was made in culture mediato get final assay concentrations of 100, 10, 1, 0.1 and 0.01 μg/ml, and1, 0.1, 0.01, 0.001 and 0.0001%, respectively.

Cell Line and Culture Media.

The tumor cell line, A431 (human epidermoid carcinoma), obtained fromAmerican Type Culture Collection (ATCC CRL-1555), was incubated in anair atmosphere of 5% CO₂ at 37° C. The culture medium was used withDulbecco's Modified Eagle's medium, 90%; Fetal Bovine Serum, 10% andsupplemented with 1% Antibiotic-Antimycotic.

Chemicals.

The following chemicals were used in the assay: AlamarBlue (Biosource,USA), Antibiotic-Antimycotic (GIBCO BRL, USA), Dulbecco's ModifiedEagle's Medium (GIBCO BRL, USA), Fetal Bovine Serum (HyClone, USA), andMitomycin (Kyowa, Japan).

Equipment.

The following equipment was used in the assay: CO₂ Incubator (Form aScientific Inc., USA), Centrifuge 5810R (Eppendorf, Germany),Hemacytometer (Hausser Scientific Horsham, USA), Inverted MicroscopeCK-40 (Olympus, Japan), System Microscope E-400 (Nikon, Japan),Spectrafluor Plus (Tecan, Austria), and Vertical Laminar Flow (TsaoHsin, R.O.C.).

Methods.

The anti-proliferation for the test substances was evaluated. Aliquotsof 100 pl of cell suspension (about 3×10³/well) were placed in 96-wellmicrotiter plates in an atmosphere of 5% CO₂ at 37° C. After 24 hours,100 pl of growth medium and 2 pl of test solution, Mitomycin or vehicle(distilled water) were added respectively per well in duplicate for anadditional 72-hour incubation. Two test compounds, leaf extract androast leaf, were evaluated at concentrations of 100, 10, 1, 0.1 and 0.01pg/ml. The other compound, leaf juice, was evaluated at concentrationsof 1, 0.1, 0.01, 0.001 and 0.0001%. At the end of incubation, 20 pl of90% alamarBlue reagent was added to each well for another 6-hourincubation before detection of cell viability by fluorescent intensity.Fluorescent intensity was measured using a Spectrafluor Plus platereader with excitation at 530 nm and demission at 590 nm.

IC₅₀, TGI, and LC₅₀ values were then determined. IC₅₀ (50% InhibitionConcentration) is the test compound concentration where the increasefrom time_(o) in the number or mass of treated cells was only 50% asmuch as the corresponding increase in the vehicle-control at the end ofthe experiment. TGI (Total Growth Inhibition) is the test compoundconcentration where the number or mass of treated cells at the end ofthe experiment was equal to that at time₀. LC₅₀ (50% LethalConcentration) is the test compound concentration where the number ormass of treated cells at the end of the experiment was half that attime₀. The measured results were calculated by the following formula:

PG(%)=100×(Mean F _(test)−Mean F _(time0))^(/)(Mean F _(ctr l)−Mean F_(time0))

If (Mean F_(test)−Mean F_(time0))^(<0), then

PG(%)−100×(Mean F _(test)−Mean F _(time0))/(Mean F _(time0)−Mean F_(blank))

Where: PG=percent growth; Mean F_(time0)=The average of 2 measuredfluorescent intensities of reduced alamarBlue at the time just beforeexposure of cells to the test substance; Mean F_(test)=The average of 2measured fluorescent intensities of alamarBlue after 72-hour exposure ofcells to the test substance; Mean F_(ctrl)=The average of 2 measuredfluorescent intensities of alamarBlue after 72-hour incubation withoutthe test substance; and Mean F_(blank)=The average of 2 measuredfluorescent intensities of alamarBlue in medium without cells after72-hour incubation.

A decrease of 50% or more (≧50%) in fluorescent intensity relative tothe vehicle-treated control indicated significant cell growthinhibition, cytostatic or cytotoxic activity, and a semi-quantitativeIC₅₀, TGI, and LC₅₀ were then determined by nonlinear regression usingGraphPad Prism (GraphPad Software, USA).

Results.

The following tables summarize the results of the assay.

Effect of Morinda Citrifolia Test Substances on the Growth of A431 SkinTumor Cells

TABLE 7 Percent Grown (Mean = SEM, n = 2) Test Assay Concentration(111/m1) Substance Name A Blank Time 0 ^(u)Vehicle 100 10 1 0.1 0.01Leaf Extract Skin −100 0 100 46 +/− 1 72 +/− 5 89 +/− 1 88 +/− 3 101 +/−7 Roast Leaf Skin −100 0 100 72 +/− 5 79 +/− 4 87 +/− 2 91 +/− 6  99 +/−5

TABLE 8 Percent Grown Test Assay Concentration (%) Substance Name BlankTime 0 Vehicle 1 0.1 0.01 0.001 0.001 Leaf Juice Skin −100 0 100 74 +/−2 83 +/− 2 77 +/− 2 83 +/− 2 94 +/− 1 Roast Leaf Skin −100 0 100 72 +/−5 79 +/− 4 87 +/− 2 91 +/− 6 94 +/− 5

TABLE 9 Percent Grown Test Assay Concentration (ttM) Substance NameBlank Time 0 Vehicle 10 1 0.1 0.01 0.001 Mitomycin Skin −100 0 100 97+/− 0 35 +/− 8 7 +/− 3 82 +/− 3 101 +/− 5A decrease of 50% or more (≧50%) in fluorescent intensity relative tovehicle-treated control indicates significant growth inhibition,cytostatic or cytotoxic activity. As utilized in tables 7-10, thefollowing terms mean:Blank: In duplicate, average fluorescent intensity of alamarBlue inmedium without cells after 3-day incubation period relative to time_(d)(transformed and recorded as −100%).Time₀: In duplicate, average fluorescent intensity of alamarBlue inmedium just before exposure of cells to test substance (transformed andrecorded as 0%).Vehicle: In duplicate, average fluorescent intensity of alamarBlue inmedium containing cells and added vehicle after 3-day incubation periodrelative to time_(d) (transformed and recorded as 100%).Mso (50% Inhibition Concentration): Test compound concentration wherethe increase from time_(d) in the number or mass of treated cells wasonly 50% as much as the corresponding increase in the vehicle-control atthe end of experiment.TGI (Total Growth Inhibition): Test compound concentration where thenumber or mass of treated cells at the end of experiment was equal tothat at timed.LC₅₀ (50% Lethal Concentration): Test compound concentration where thenumber or mass of treated cells at the end of experiment was half thatat timed.The following figures are concentration-response curves for inhibitionof growth in A431 human tumor cell line treated with Leaf Extract, LeafJuice and Roast Leaf.

IC₅₀ TG₁ and LC₅₀ Values of Morinda Citrifolia Test Compounds

TABLE 10 Compound Assay Name aic50 bTGI c1_, Cso Leaf Extract Tumor,Skin 76 μg/ml >100 μg/ml >100 μg/ml Leaf Juice Tumor, Skin 0.20% 0.36%0.65% Roast Leaf Tumor, Skin >100 μg/ml >100 μg/ml >100 μg/ml MitomycinTumor, Skin 0.035 μM 0.19 μM 1.0 μIVI

A semi-quantitative determination of IC₅₀ TG₁ and LC₅₀ was carried outby nonlinear regression analysis using GraphPad Prism (GraphPadSoftware, USA).

In summary, some embodiments of the present invention provide using Nonileaf juice and Noni leaf extract to inhibit: HMG-CoA Reductase; PDE3 andPDE4; 5-LOX and 15-LOX; XO; GABA and the growth of the second mostcommon human skin cancer cell line, for the purpose of: alleviating painand inflammation; treating prostate cancers; lower cholesterol levels;counteracting Diabetes Type II; maintaining the highest possibleintegrity of cellular interactions in the brain resulting in anundisturbed neural function, (i.e. neuroprotection); ameliorating theeffects of asthma and allergies; improving energy; improving insulinsecretion; decreasing kidney stone accumulation; alleviating the effectsof gout; minimizing convulsions related to epilepsy and other seizuredisorders; and providing palliative effects to those addicted to drugs.

Example 4

Additionally, the squeezed juice from fresh Morinda citrifolia leaf wasutilized to identify by bio-assay on Adenosine A2A four bio-activecompounds which have been isolated and identified to have significantbioactivity. Their structures have been determined by NMR techniques andmass spectrometry and they have been identified as Pyro-phorbide a,Pheoporbide a, Purpin 7, and Pheophorbide Phytolester. The isolation andcharacterization of the above referenced bioactive compounds provides asignificant explanation for the anti-inflammatory and analgesicproperties of extracts derived from the Morinda citrifolia plant,particularly from the leaf of the plant.

The present invention may be embodied in other specific forms withoutdeparting from its spirit of essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims, rather than by the foregoing description. Allchanges that come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

1. A method of treating inflammation in a mammal, which comprises:acquiring Morinda citrifolia leaves; dissolves cutting the leaves intosmall pieces; placing the leaves into a crushing device; crushing theleaves; percolating the leaf pieces in an alcohol solution; collectingthe alcohol and all alcohol soluble ingredients from the alcohol leafslurry; allowing the alcohol to evaporate; leaving a primary leafextract; dissolving the leaf extract in water; and administering to saiddiluted leaf extract mammal a compound containing an effective amount ofa processed Morinda citrifolia leaf product wherein said compounddecreases or prevents inflammation and/or pain.
 2. The method of claim1, wherein the leaf extract is dissolved in water to dilute the solutionby an amount selected from a list consisting of: 10,000 milligrams permilliliter, 1000 milligrams per milliliter 100 milligrams permilliliter, 10 milligrams per milliliter, 1 milligram per milliliter,0.1 milligrams per milliliter, 0.001 milligrams per milliliter, and0.0001 milligrams per milliliter.
 3. The method of claim 1, wherein theprimary leaf extract is pasteurized.
 4. The method of claim 1, whereinthe primary leaf extract is partially sterilized.
 5. The method of claim1, further comprising a step of placing the primary leaf extract in acentrifuge to remove any remaining leaf juice and other materials,including chlorophyll.
 6. The method of claim 1, wherein the primaryleaf extract is further fractionated into a fraction selected from alist consisting of: a dry hexane fraction; and an aqueous methanolfraction hexane.
 7. The method of claim 6, wherein the secondaryfractions are produced utilizing a gas chromatograph containing siliconedioxide.
 8. The method of claim 6, further comprising the steps ofdividing the secondary methanol fraction into additional methanolfractions.
 9. The method of claim 6, wherein the secondary hexanefraction is further fractionated into additional hexane fractions. 10.The method of claim 1, further comprising a step of combining the leafextract with the fruit juice of the fruit of the Morinda citrifoliaplant to obtain a leaf and serum.
 11. The method of claim 2, furthercomprising the step of combining the primary extract with a carriermedium prior to administration.
 12. The method of claim 1, whereinCyclooxygenase-2 is also selectively inhibited, relative toCyclooxygenase-1.
 13. The method of claim 1, wherein the decreasing orprevention of inflammation and/or pain is accomplished while maintaininggastric mucosal integrity.
 14. The method of claim 1, further comprisingthe step of diluting the dissolved extract by 100-fold prior toadministration.
 15. A method for promoting health comprising the stepsof: adding a processed Morinda citrifolia component to an alcohol-basedsolution; isolating and extracting an active ingredient of saidprocessed Morinda citrifolia component from said solution to obtain afraction; introducing said extracted active ingredient into said mammal,wherein said extracted active ingredient decreases or preventsinflammation and/or pain.
 16. The method of claim 15, wherein saidalcohol-based solution is selected from the group consisting essentiallyof methanol, ethanol, and ethyl acetate, and other alcohol-basedderivatives.
 17. The method of claim 1, wherein said active ingredientis selected from a list consisting of Pyro-phorbide a, Pheoporbide a,Purpin 7, and Pheophorbide Phytolester. 18.-28. (canceled)